Bone morphogenetic proteins (BMPs) play pivotal roles in the regulation of skin development. To study the role of BMPs in skin tumorigenesis, BMP antagonist noggin was used to generate keratin 14-targeted transgenic mice. In contrast to wild-type mice, transgenic mice developed spontaneous hair follicle-derived tumors, which resemble human trichofolliculoma. Global gene expression profiles revealed that in contrast to anagen hair follicles of wild-type mice, tumors of transgenic mice showed stage-dependent increases in the expression of genes encoding the selected components of Wnt and Shh pathways. Specifically, expression of the Wnt ligands increased at the initiation stage of tumor formation, whereas expression of the Wnt antagonist and tumor suppressor Wnt inhibitory factor-1 decreased, as compared with fully developed tumors. In contrast, expression of the components of Shh pathway increased in fully developed tumors, as compared with the tumor placodes. Consistent with the expression data, pharmacological treatment of transgenic mice with Wnt and Shh antagonists resulted in the stage-dependent inhibition of tumor initiation, and progression, respectively. Furthermore, BMP signaling stimulated Wnt inhibitory factor-1 expression and promoter activity in cultured tumor cells and HaCaT keratinocytes, as well as inhibited Shh expression, as compared with the corresponding controls. Thus, tumor suppressor activity of the BMPs in skin epithelium depends on the local concentrations of noggin and is mediated at least in part via stage-dependent antagonizing of Wnt and Shh signaling pathways.

We identified human visual field maps, LO1 and LO2, in object-selective lateral occipital cortex. Using transcranial magnetic stimulation (TMS), we assessed the functions of these maps in the perception of orientation and shape. TMS of LO1 disrupted orientation, but not shape, discrimination, whereas TMS of LO2 disrupted shape, but not orientation, discrimination. This double dissociation suggests that specialized and independent processing of different visual attributes occurs in LO1 and LO2.

Recent casework in Belgium involving the search for human remains buried with lime, demonstrated the need for more detailed understanding of the effect of different types of lime on cadaver decomposition and its micro-environment. Six pigs (Sus scrofa) were used as body analogues in field experiments. They were buried without lime, with hydrated lime (Ca(OH)(2)) and with quicklime (CaO) in shallow graves in sandy loam soil in Belgium and recovered after 6 months of burial. Observations from these field recoveries informed additional laboratory experiments that were undertaken at the University of Bradford, UK. The combined results of these studies demonstrate that despite conflicting evidence in the literature, hydrated lime and quicklime both delay the decay of the carcass during the first 6 months. This study has implications for the investigation of clandestine burials and for a better understanding of archaeological plaster burials. Knowledge of the effects of lime on decomposition processes also has bearing on practices involving burial of animal carcasses and potentially the management of mass graves and mass disasters by humanitarian organisations and DVI teams.

We identify cytochrome P450 1A1 (CYP1A1) as a target for tumor-selective drug development in bladder cancer and describe the characterization of ICT2700, designed to be metabolized from a prodrug to a potent cytotoxin selectively by CYP1A1. Elevated CYP1A1 expression was shown in human bladder cancer relative to normal human tissues. RT112 bladder cancer cells, endogenously expressing CYP1A1, were selectively chemosensitive to ICT2700, whereas EJ138 bladder cells that do not express CYP1A1 were significantly less responsive. Introduction of CYP1A1 into EJ138 cells resulted in 75-fold increased chemosensitivity to ICT2700 relative to wild-type EJ138. Negligible chemosensitivity was observed in ICT2700 in EJ138 cells expressing CYP1A2 or with exposure of EJ138 cells to CYP1B1- or CYP3A4-generated metabolites of ICT2700. Chemosensitivity to ICT2700 was also negated in EJ138-CYP1A1 cells by the CYP1 inhibitor alpha-naphthoflavone. Furthermore, ICT2700 did not induce expression of the AhR-regulated CYP1 family, indicating that constitutive CYP1A1 expression is sufficient for activation of ICT2700. Consistent with the selective activity by CYP1A1 was a time and concentration-dependent increase in gamma-H2AX protein expression, indicative of DNA damage, associated with the activation of ICT2700 in RT112 but not EJ138 cells. In mice-bearing CYP1A1-positive and negative isogenic tumors, ICT2700 administration resulted in an antitumor response only in the CYP1A1-expressing tumor model. This antitumor response was associated with detection of the CYP1A1-activated metabolite in tumors but not in the liver. Our findings support the further development of ICT2700 as a tumor-selective treatment for human bladder cancers.

PURPOSE: Epidemiologic research has shown that multifocal spectacle wearers (bifocal and progressive addition lenses [PALs]) are more than twice as likely to fall than are nonmultifocal spectacle wearers, with this risk further increasing when negotiating stairs. The present study investigated whether step and stair descent safety is improved by using single-vision distance lenses. METHODS: From a stationary standing position on top of a block, 20 long-term multifocal wearers stepped down (from different block heights) onto a lower level wearing bifocal, progressive addition, or single-vision distance lenses. RESULTS: Use of single-vision distance spectacles led to an increased single-limb support time, a reduced ankle and knee angle and vertical center-of-mass velocity at contact with the lower level, and a reduced ankle angular velocity and vertical center-of-mass velocity during initial landing (P < 0.03). These findings indicate that landing occurred in a more controlled manner when the subjects wore single-vision distance spectacles, rather than tending to "drop" onto the lower level as occurred when wearing bifocals or PALs. CONCLUSIONS: Use of single-vision distance spectacles led to improvements in landing control, consistent with individuals' being more certain regarding the precise height of the lower floor level. This enhanced control was attributed to having a view of the foot, step edge, and immediate floor area that was not blurred, magnified, or doubled and that did not suffer from image jump or peripheral distortions. These findings provide further evidence that use of single-vision distance lenses in everyday locomotion may be advantageous for elderly multifocal wearers who have a high risk of falling.

The overarching theme of the book is differential treatment in death, which is examined at the site-specific, settlement, regional and national level. More specifically, the symbolism of conversion-period grave good deposition, the impact of the church, and aspects of identity, burial diversity and biocultural approaches to cemetery analysis are discussed.

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